Scientist of the month

November 2016

Alan Leonard

Alan Leonard

Dr. Leonard’s research interests are focused on the regulatory mechanisms that control normal cell growth, particularly the cell cycle-specific assembly of protein complexes that trigger new rounds of chromosome replication.

Members of his laboratory (with Dr. Juila Grimwade) have developed methods for high-resolution analysis of regulatory complexes in synchronously-dividing and non-synchronous cell populations. Although the studies are primarily focused on bacterial cells, the technology is appropriate for all cell types. Our goal is to understand important cellular machinery and identify new targets for antibacterial compounds.

Our ongoing studies are focused on important stages in the ordered assembly of E. coli pre-replication complexes, and we established that low affinity initiator protein (DnaA)-replication origin DNA (oriC) interactions are the rate-limiting step in the initiation process. We also found that DNA bending makes these interactions switch-like.

Some of the low affinity DnaA binding sites also have a 3-4 fold preference for DnaA-ATP and are positioned into two convergent, helically-phased arrays. Our current model suggests that DnaA bound to high affinity sites nucleates DnaA-ATP oligomers that grow progressively along the DNA, directed by the low affinity sites. Studies are currently underway to identify the stages of orisome assembly that require DnaA oligomerization.​